Phenytoin with isoniazid

The use of stavudine in combination with isoniazid, vincristine, phenytoin and ethambutol may increase the risk of peripheral neuropathy and pancreatitis. It competes with zidovudine for phosphorylation and should not be used in combination. 

Ethosuximide Ethosuximide interacts with isoniazid, phenytoin, phenobarbi-tone, carbamazepine, valproic acid, antipsychotics, and antidepressants.193... 

Increased effect with isoniazid, nicotinamide, phenytoin Decreased effect with carbamazepine, ethosuximide... 

The interaction with phenytoin and isoniazid alone is well documented, well established, clinically important and potentially serious. About 50% of the population are slow or relatively slow metabolisers of isoniazid, but not all of them develop serum phenytoin levels in the toxic range. The reports indicate that somewhere between 10 and 33% of patients are at risk. This adverse interaction may take only a few days to develop fully in some patients, but several weeks in others. Therefore concurrent use should be very closely monitored, making suitable dosage reductions as... 

Phenytoin interacts widi many different drugp. For example isoniazid, chloramphenicol, sulfonamides, benzodiazepines, succinimides, and cimetidine all increase phenytoin blood levels. The barbiturates, rifampin, theophylline, and warfarin decrease phenytoin blood levels. When administering the hydantoins with meperidine, die analgesic effect of meperidine is decreased. 

The following drugp have a decreased pharmacologic effect when administered with an antacid corticosteroids, digoxin, chlorpromazine, oral iron products, isoniazid, phenothiazines, ranitidine, phenytoin, valproic acid, and the tetracyclines. 

Drugs that may interact with zalcitabine include antacids, chloramphenicol, cisplatin, dapsone, didanosine, disulfiram, ethionamide, glutethimide, gold, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, vincristine, cimetidine, metoclopramide, amphotericin, aminoglycosides, foscarnet, antiretroviral nucleoside analogs, pentamidine, and probenecid. 

Folate deficiency can be dietary, especially in the eiderly, due to increased demand like in pregnancy, or due to maiabsorption syndromes. Agents which can cause folic acid deficiency with long-term use include phenytoin, oral contraceptives, isoniazid and glucocorticosteroids. In rare instances the use of dihydrofolate reductase inhibitors like trimethoprim, methotrexate or pyrimethamine can contribute to the occurrence of folate deficiency. Folinic acid can circumvent the need for the inhibited dihydrofolate reductase. 

Isoniazid inhibits cytochrome P450 enzyme function and thus can interact with drugs that are subject to cytochrome P450 mediated metabolism like warfarin and the antiepileptic agents phenytoin and car-bamazepine. 

Only a few well-documented drug combinations with phenytoin may necessitate dosage adjustment. Coadministration of the following drugs can result in elevations of plasma phenytoin levels in most patients cimetidine, chloramphenicol, disulfiram, sulthiame, and isoniazid (in slow acetylators). Phenytoin often causes a decline in plasma carbamazepine levels if these two drugs are given concomitantly. 

Certain concomitantly administered drugs may interfere with the effectiveness of the oral contraceptives or lead to an increased incidence of breakthrough bleeding. These include rifampin, isoniazid, ampiciUin, neomycin, penicillin V, chloramphenicol, sulfonamides, nitrofurantoin, phenytoin, barbiturates, primidone, analgesics, and phenothiazines. 

Isoniazid [NP] Increased serum phenytoin problem primarily with slow acetylators of isoniazid. 

Folic acid deficiency can be caused by drugs that interfere with folate absorption or metabolism. Phenytoin, some other anticonvulsants, oral contraceptives, and isoniazid can cause folic acid deficiency by interfering with folic acid absorption. Other drugs such as methotrexate and, to a lesser extent, trimethoprim and pyrimethamine, inhibit dihydrofolate reductase and may result in a deficiency of folate cofactors and ultimately in megaloblastic anemia. 

Isoniazid Isoniazid is incompatible with sugars. Isoniazid overdose may be severe to fatal, and treatment is symptomatic and supportive, including stomach wash for control of convulsions and treating metabolic acidosis. Administration of pyridoxine and hemodialysis may be needed. Isoniazid interacts with carba-mazepine, phenytoin, diazepam, triazolam, chlorzoxazone, theophylline, ethosux-imide, enflurane, cycloserine, and warfarin. 

Correct choice = D. Isoniazid reacts with pyri-doxine (vitamin Be), which can cause a deficiency of this vitamin, isoniazid readily penetrates into infected cells and therefore is effective against bacilli growing intracellulariy. Isoniazid inhibits the metabolism of phenytoin. 

Type III reactions are caused by tissue injury due to immune complexes. The antigen-antibody complexes are usually cleared by the immune system however, repeated contact with antigens can cause the complex to deposit in tissue and result in tissue injury. Serum sickness is the classic example of a Type III reaction. Medications associated with serum sickness include many antibiotics, phenytoin, salicylates, barbiturates, nonsteroidal antiinflammatory drugs, isoniazid, antisera, hydralazine, captopril, and sulfonamides. Procainamide-induced lupus, described in Chapter 16, is also considered a Type III reaction. 

Piperonyl butoxide, isoniazid, and SKF 525A and related chemicals are inhibitors of various xenobiot-ic-metabolizing enzymes. For instance, piperonyl butoxide increases the toxicity of pyrethrum (an insecticide) by inhibiting MFO activity in insects that detoxifies this agent. Isoniazid, when taken along with phenytoin, lengthens the plasma half-life of the antiepileptic drug and increases its toxicity. Iproniazid inhibits monoamine oxidase and increases the cardiovascular effects of tyramine, which is found in cheese and which is normally readily metabolized by the oxidase. 

Clinically important, potentially hazardous interactions with aluminum, aminophylline, carbamazepine, carbimazole, cyclosporine, daclizumab, diuretics, etoposide, etretinate, grapefruit juice, indomethacin, isoniazid, itraconazole, ketoconazole, licorice, live vaccines, methotrexate, naproxen, oral contraceptives, pancuronium, phenobarbital, phenytoin, rifampicin, troleandomycin... 

The following drugs have been commonly associated with inducing, aggravating or unmasking SLE beta-blockers, carbamazepine, chlorpromazine, estrogens, griseofulvin, hydralazine, isoniazid (INH), lithium, methyldopa, minoxidil, oral contraceptives, penicillamine, phenytoin (diphenylhydantoin), procainamide, propylthiouracil, quinidine, and testosterone. 

These can interfere with vitamin processing in the intestinal tract, tie up the vitamin preventing it from being used, or possibly promote elimination of the vitamin. Examples include isoniazid-pyridoxine, phenobarbital-cholecalciferol, methotrexate-folic acid, phenytoin-folicacid. 

Dantrolene, isoniazid, phenytoin, nitrofurantoin, and trazodone have been reported in association with a type of autoimmune-mediated disease in the liver. Patients experience periods of symptomatic hepatitis followed by periods of convalescence, only to repeat the experience months later. It is a progressive disease with a high mortality rate and is more common in females than males. Antinuclear antibodies appear in most patients. These drugs appear to form... 

Transient elevations of the serum transaminases occur in 12% to 15% of patients receiving isoniazid and usually occur within the first 8 to 12 weeks of therapy. Overt hep ato toxicity, however, occurs in only 1% of cases. Risk factors for hepatotoxicity include patient age, preexisting liver disease, excessive alcohol intake, pregnancy, and the postpartum state. Isoniazid also may result in neurotoxicity, most frequently presenting as peripheral neuropathy or, in overdose, as seizures and coma. Patients with pyridox-ine deficiency, such as pregnant women, alcoholics, children, and the malnourished, are at increased risk. Isoniazid may inhibit the metabolism of phenytoin, carbamazepine, primidone, and warfarin." Patients who are being treated with these agents should be monitored closely, and appropriate dose adjustments should be made when necessary. 

Isoniazid in combination with phenytoin Central nervous system toxicity Slow acetylator... 

Folic acid deficiency can occur due to pregnancy, malabsorption syndromes or inadequate diet. Some drugs, for example phenytoin (used in epilepsy), oral contraceptives and isoniazid (used in treating tuberculosis), can cause reduced absorption of folic acid. Oral replacement therapy with folic acid is effective. 

Because benzodiazepines do not significantly induce the synthesis of hepatic CYPs, chronic benzodiazepine administration usually does not result in the accelerated metabolism of benzodiazepines or other substances. Cimetidine and oral contraceptives inhibit N-dealkylation and 3-hydroxylation of benzodiazepines, as do ethanol, isoniazid, and phenytoin to a lesser degree. These reactions usually are reduced to a greater extent in elderly patients and in patients with chronic liver disease than are those involving conjugation. 

---